This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neural crest cells detach from the embryonic neural tube and then migrate extensively throughout the embryo before differentiating into a number of derivatives. A subset of neural crest cells, called cardiac neural crest cells, contribute to several aspects of heart development, including septation, myocardial differentiation, and proper formation of the outflow tract. Many congenital heart defects are associated with abnormal cardiac neural crest cell development. However, very little is known about the factors that regulate cardiac neural crest migration in the embryo. We have shown the secreted protein TIMP-2 is expressed by chicken cardiac NC cells and required for their normal development. This project tests the hypothesis that TIMP-2 directs cardiac NC cells into the proper migratory pathway, and will elucidate the mechanism by which it does so.